Permanent loss of cardiomyocytes and scar tissue formation after myocardial infarction (MI) results in an irreversible damage to the cardiac function. Cardiac repair (replacement, restoration, and regeneration) is, therefore, essential to restore function of the heart following MI. Existing therapies lower early mortality rates, prevent additional damage to the heart muscle, and reduce the risk of further heart attacks. However, there is need for treatment to improve the infarcted area by replacing the damaged cells after MI. Thus, the cardiac tissue regeneration with the application of stem cells may be an effective therapeutic option. Recently, interest is more inclined toward myocardial regeneration with the application of stem cells. However, the potential benefits and the ability to improve cardiac function with the stem cell-based therapy need to be further addressed. In this review, we focus on the clinical applications of stem cells in the cardiac repair.

Renin inhibitors are antihypertensive drugs that block the first step in the renin-angiotensin system. Their mechanism of action differs from that of the angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists, but like these drugs, renin inhibitors interrupt the negative feedback effects of angiotensin II on renin secretion. The renin-angiotensin-aldosterone system (RAAS) has long been recognized to play a significant role in hypertension pathophysiology. Certain agents that modify the RAAS can control blood pressure and improve cardiovascular outcomes. Optimization of this compound by Novartis led to the development of aliskiren - the only direct renin inhibitor which is clinically used as an antihypertensive drug. Aliskiren is the first of a new class of antihypertensive agents. Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing. In short-term studies, it was effective in lowering blood pressure either alone or in combination with valsartan and hydrochlorothiazide, and had a low incidence of serious adverse effects. It was approved by the Food and Drug Administration in 2007 for the use as a monotherapy or in combination with other antihypertensives. Greater reductions in blood pressure have been achieved when aliskiren was used in combination with hydrochlorothiazide or an angiotensin-receptor blocker. The most common adverse effects reported in clinical trials were headache, fatigue, dizziness, diarrhea, and nasopharyngitis. Aliskiren has not been studied in patients with moderate renal dysfunction; as an RAAS-acting drug, it should be prescribed for such patients only with caution.

Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

Roll compaction was applied for the preparation of hydroxypropyl cellulose (HPC)-based sustained-release matrix tablets. Matrix tablets made via roll compaction exhibited higher dosage uniformity and faster drug release than direct-compacted tablets. HPC viscosity grade, roll pressure, and milling speed affected tablet properties significantly. Roll compaction seems to be an adequate granulation method for the preparation of HPC-based matrix tablets due to the simplicity of the process, less handling difficulty from HPC tackiness as well as easier particle size targeting. Selecting the optimum ratio of plastic excipients and the particle size of starting materials can however be critical issues in this method.

Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata), in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C) residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues). Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

Aim: This study was designed to examine the chemical composition and in vitro antimicrobial potential of methanolic extract of Psidium guajava Linn (Myrtaceae). Materials and Methods: The inhibitory effect of methanolic extract of P. guajava was tested against three bacterial and two fungal strains by using the paper disc diffusion method. Results: The methanolic extract exhibited antibacterial activity against E. coli with minimum inhibitory concentration, 0.78 μg/ml, minimum bactericidal concentration of 50 μg/ml, and appreciable antifungal activity with minimum inhibitory concentration of 12.5 μg/ml. Preliminary phytochemical analysis of methanolic extract revealed the presence of antimicrobial compounds such as flavonoids, steroids, and tannins, which may contribute for the antimicrobial action of P. guajava.Conclusion: The extract was found to be bacteriostatic and fungistatic in action.

Objectives: The primary objective of this study was to investigate the antihyperlipidemic effect of the chloroform (CETC) and methanol (METC) extracts of leaves of Trichilia connaroides in hypercholesterolemic rats and, subsequently, to evaluate the possible mechanism of its antihyperlipidemic effect. Materials and Methods: The antihyperlipidemic activity of CETC and METC (100 mg/kg) in hypercholesterolemic rats was investigated by recording the serum lipid profile after a month-long oral treatment of these extracts. Further, hypercholesterolemic regression test and hypercholesterolemic progression test were carried out to understand the possible mechanism of its antihypercholesterolemic effect. The data were analyzed for statistical significance by one-way ANOVA, followed by Dunnet's test. Results and Conclusion: Hypercholesterolemic rats treated with CETC and METC produced a significant fall (P<0.05) in plasma triglyceride, total cholesterol, very low density lipoprotein (VLDL )-cholesterol and low density lipoprotein (LDL)-cholesterol and rise (P < 0.05) in high density lipoprotein (HDL) -cholesterol. A significant reduction (P < 0.01) in atherogenic index, increase (P < 0.05) in body weight and an insignificant influence on food intake were also observed at the end of the study. A hypercholesterolemic regression test revealed a significant reduction (P < 0.05) in the serum cholesterol level in both CETC and METC extract-treated animals. During the hypercholesterolemic progression test, a similar reduction in the serum cholesterol level was observed only in the METC extract-treated animals. The antihyperlipidemic effect was similar to fenofibrate and ezitimibe. Significant changes in the lipid profile in hypercholesterolemic animals confirm a potential antihyperlipidemic activity of the extracts. The CETC and METC extracts influenced the absorption and metabolism of dietary cholesterol to elicit the antihyperlipidemic effect.

Background: Peptic ulcer is a global health problem of the gastrointestinal tract characterized by mucosal damage secondary to pepsin and gastric acid secretion which occurs due to due to an imbalance between offensive and defensive factors. Objective: The present study was carried out with methanolic extract of the seed coat of Tamarindus indica Linn. to evaluate its antiulcer potential on ibuprofen, alcohol and pyloric ligation induced gastric lesions. Materials and Methods: Doses of 100 mg/kg & 200 mg/kg of methanolic extract wre administered orally to rats of different groups. Ranitidine at a dose of 50 mg/kg was used as a standard drug for these gastric ulcer models. The gastric content was collected and the volume was measured. The ulceration index was determined by examining the inner lining of each stomach. Furthermore, the effect was assessed by free acidity, pepsin activity, total carbohydrate (TC), protein content (PK). Result: The result showed that the methanolic extract of seed coats of Tamarindus indica significantly reduce the total volume of gastric juice, free and total acidity of gastric secretion (P < 0.01) in pylorus ligation induced ulcer model as is comparable with the standard drug ranitidine. There was also a significant reduction in ulcer index (P < 0.01) as compared to control group. Conclusion: The methanolic extracts of seed coat of Tamarindus indica can be used as a new source of antiulcer agent in animals.

Objective: To investigate the medicative effects of medium-polar (benzene:acetone, 1:1, v/v) extract of leaves from Stevia rebaudiana (family Asteraceae) on alloxan-induced diabetic rats. Materials and Methods: Diabetes was induced in adult albino Wistar rats by intraperitoneal (i.p.) injection of alloxan (180 mg/kg). Medium-polar extract was administered orally at daily dose of 200 and 400 mg/kg body wt. basis for 10 days. The control group received normal saline (0.9%) for the same duration. Glibenclamide was used as positive control reference drug against Stevia extract. Results: Medium-polar leaf extract of S. rebaudiana (200 and 400 mg/kg) produced a delayed but significant (P < 0.01) decrease in the blood glucose level, without producing condition of hypoglycemia after treatment, together with lesser loss in the body weight as compared with standard positive control drug glibenclamide. Conclusions: Treatment of diabetes with sulfonylurea drugs (glibenclamide) causes hypoglycemia followed by greater reduction in body weight, which are the most worrisome effects of these drugs. Stevia extract was found to antagonize the necrotic action of alloxan and thus had a re-vitalizing effect on β-cells of pancreas.

Objectives: Standardization is essentially a measure for ensuring the quality control of herbal drugs. But the gender of the plant affecting the quality of crude drugs does not appear to have been taken care of so far. Today, sophisticated modern research tools for the evaluation of the plant drugs are available but the microscopic method is one of the simplest and cheapest methods. Methods and Materials: The pharmacognostic investigation of the fresh, powdered, and anatomical sections of the female leaves of Trichosanthes dioica Roxb. was carried out to determine its bioprospective constants. Results and Discussion : Externally, the leaves possess a cordate base, a sinuate and dentate margin, an acute to acuminate apex, and both surfaces are very rough with rigid hair surface. Internally, it shows the presence of anomocytic stomata, unicellular, and both glandular and simple covering trichomes scattered as such throughout or attached with the cells of the epidermis. Majority of the glandular trichomes are with a four-to-five-celled uniseriate stalk and unicellular head; very few are short and with uni- to bicellular stalk and uni- to multicellular head especially from that of the petiole region. Simple covering, multicellular, uniseriate thick-walled trichomes are of various sizes. Usually cells of both simple and glandular trichomes are often embedded with cystolith. Phytochemical studies of the powdered leaves revealed the presence of alkaloids, resins, glycosides, flavonoids and some carbohydrates. The pharmacognostic profile of the leaves will assist in the standardization for quality, purity, and sample identification.

Background: Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy. Materials and Methods: Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD 50 and CD 99 values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100-300 mg/kg), lamotrigine (3-12 mg/kg) and flunarizine (5-20 mg/kg), and then each group of mice was injected with CD 99 dose of PTZ (65mg/kg i.p.). Another group of mice received single ED 50 dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal-Wallis ANOVA on Ranks test. Results: As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection. Conclusion: As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.

Introduction: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K) channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. Materials and Methods: The synthesis of 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR, 1 H, 13 C NMR, FAB Mass and nitrogen analysis. These synthesized compounds (6a-o) were then evaluated for anti-inflammatory activity by carrageenan induced paw edema method.Out of these synthesized compounds, some (6f, i and k) were evaluated for antinociceptive activity by Hot plate method and Tail immersion method. Results and Discussion: The synthesis of 4-(substituted amino)-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) was accomplished. The IR spectra exhibited characteristic bands for C-N, C=N, SH and C=O at 1350-1360, 1511-1548, 2520-2594.3 and 1650-1719 cm -1 . The C-O-C asymmetric and symmetric str. was at 1250-1254 and 1027-1079.3 cm -1 respectively. In 1 H-NMR spectra, a singlet of CONH was found in the range of δ 9.92-10.18 ppm and another singlet of thiol group was observed in the range of δ 8.63-9.92 ppm. A singlet of Ar-OCH 3 was also found between δ 3.57-3.91 ppm. In 13 C- NMR spectra, C-3 and C-5 of the 1,2,4 - triazole nucleus were observed in the range of δ 147-166.9 ppm. Carbonyl carbon and methylene carbon of -NHCOCH 2 N< were found between δ 166.5-177.5 and δ 47.1-62 ppm respectively. Acute toxicity study was donr following OECD-423 and cut-off dose was found to be between 1000-1500 mg/kg body weight. At the dose level of 100 mg/kg, 6f, 6i and 6k exhibited appreciable inhibition of oedema especially 6k exhibiting a percentage of oedema inhibition of 40.28%, which was comparable to that of the standard drug indomethacin (62.50% at 10mg/kg dose). Among the compounds tested, compound 6k exhibited good anti-nociceptive activity in both methods used. Pethidine (20mg/kg body weight s.c) is used as the standard drug. Conclusion: SAR of these synthesized compounds shows that substitution with heterocyclic moiety at C-2 of the acetamido group at position 4 of the 1,2,4-triazole produces appreciable activity as compared to substitution with aliphatic moieties since among all the synthesized compounds, the most active ones are 6f, 6i and 6k that have piperdine, 1-benzyl piperazine and morpholine group, respectively at C-2 of the acetamido group at position 4 of the 1,2,4-triazole.

Background: A new approach for evaluating the optical penetration depth and testing its validity with Monte Carlo simulations and Kubelka-Munk theory is used for artificial semi-rigid tissue sensitized with natural pigments. Photodynamic therapy is a promising cancer treatment in which a photosensitizing drug concentrates in malignant cells and is activated by visible light at certain wavelength. Materials and Methods: Cheap artificial semi-rigid tissue incorporated with scattering and absorbing materials along with some other composites comparable to normal human tissue has been performed. The optical parameters as measured with different conditions and calculated with various techniques are investigated. Results: The probability of interaction of light with tissue is very high when exposed to light in presence of Cichorium pumilum and RBCs followed by photohemolysis or/and photodegradation. The optical penetration depth calculated by linear absorption coefficient ranges from 0.63 to 2.85 mm is found to be comparable to those calculated using Kubelka-Munk theory or Monte Carlo simulation (range from 0.78 to 2.42 mm). The ratio of absorption to the scattering is independent of thickness and decreases with increasing irradiation time. Moreover, the optical parameters as well as their ratios are in very good agreement in the two approaches of calculation. The values of absorption and scattering coefficients are independent of thickness. Furthermore, the average photon ranges in the samples containing no scattering and absorbing materials are about three times greater than those samples containing scattering materials. Conclusion: Our results suggest that light propagation with optical properties presented in this work could be applicable in diagnostic and therapeutic of the human biological tissue for photodynamic therapy.

Background: Ophthalmic drug delivery systems are the challenging subject for the researchers because of delicate nature of ocular membrane and preventive barriers leading to less than 1 % of Bioavailability. Reasons for reduced bioavailability are due to rapid pre corneal elimination, tear turnover, lacrimal drainage, blinking and degradation by enzymes. Less bioavailability causes short duration of action and increased frequency of administration. Materials and Methods: Timolol maleate was used as model drug. Dynamic drug release studies were used to study the polymeric hydrogels and ophthalmic inserts. Rheological studies were carried out by Brookfield Viscometer LVDV- II+. Result and Discussion: Viscosity value lies in the range of 4.08 to 31.8 cps. Drug release data was fitted to various kinetic equations such as First order plots, Higuchi plots, Peppa's exponential plots. The results shows fairly linear curve and the slope value of the Peppa's equation is less than 0.5 and hence follows the fickian diffusion. Conclusion: The developed hydrogels and inserts were therapeutically effacious, stable, non irritant and provide a sustained release of drug over 8 hours time period.

Objectives: The purpose of this study was to investigate the anticancer activity of anticancer drugs (5-fluorouracil and 6-thioguanine) in polymeric nanocapsules in the presence and in the absence of gold and iron oxide nanoparticles toward Hep2 cancer cells. Materials and Methods: MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used for quantitative measurements for the anticancer cell activity. Encapsulated drug in polyethylene terephthalate-polylactic acid copolymer (PET-co-PLA) nanocapsules in the presence and absence of gold and iron oxide nanoparticles were prepared via the W/O/W emulsification solvent-evaporation method. Morphology of the nanoparticles was characterized by transmission electron microscopy and scanning electron microscopy. Conclusion: The average size of the polymeric nanocapsules, gold nanoparticles, and iron oxide nanoparticles were found to be in range of 230-260, 18 -20 nm, 5-10 nm, respectively. The findings in this study inferred that incorporated drug in polymeric nanocapsules with gold nanoparticles and iron oxide nanoparticles show better anticancer activity when compared with encapsulated drug in polymeric nanocapsules.

A number of new porphyrin-based photosensitizers have been developed for Photodynamic Therapy (PDT) in recent years. Chlorins, which are a reduced form of porphyrins, show better potential of application since they have a stronger absorption band on the red region of the visible spectrum and, hence, a deeper penetration into tissues. We found that by using heterogeneous catalytic transfer reduction (CTR), meso-tetraphenylporphyrin (TPP) could be hydrogenated, although in modest yields, to meso-tetraphenylchlorin (TPC) in a single reaction step. Best reaction conditions were attained using formic acid or sodium phosphinate/water as hydrogen donors, tetrahydrofuran (THF) or toluene as solvent and 10% palladium on charcoal as catalyst.

The World Health Organization-recommended patient care indicators in Government Hospitals were assessed in 422 patients attending the Outpatient Department in selected hospitals of the Galle district in Southern Province. The average dispensing time (ADT), percentage of drugs actually dispensed (PDAD), percentage of drugs adequately labeled (PDAL) and patient's knowledge on correct dosage (PKCD) were compared in these selected teaching hospitals (TH), general hospitals (GHs) and district hospitals (DHs) in Galle. ADT in DH (1.16 min) and GH (1.07 min) were high when compared with ADT in TH (0.81 min). PDAD was 100% in DH, 97.79% in GH and lowest in TH (94.64%). PDAL was highest (22.66%) in TH, 17.57% in GH and lowest in DH (1.57%). PKCD was 100% in GH and lowest in DH (0%) and only 50% in TH in Galle district. We noted that there was a significant difference in ADT in all three categories (P < 0.05). We noted that dispensers spend only a short dispensing time and showed a tendency for dispensing errors. We found that PDAL was very low in all hospitals but PDAD was significantly high. Even though the ADT was high in DH, PKCD was 0% due to negligence in dispensing practices. We also noted a 100% PKCD only in GH due to the practice of a well-prepared correct labeling system in GH. We noticed that these patients were provided drugs with inadequate labeling and that patients had only a poor knowledge about the drug administration schedule. We conclude that there was a low dispenser-patient ratio in all three hospitals and that there was a need for an implementation plan for proper dispensing techniques by introducing a well-prepared drug labeling system in a printed format.

Herbs have been used for medicinal purposes for centuries. According to recent investigations, they may help reduce the risk of chronic diseases, cardiovascular disease, and cancer due to antioxidant properties, which in turn can be attributed to the various phytoconstituents. With this intention, evaluation of antioxidant activity was performed. Methanol extract of aerial parts of Artemisia pallens Wall was screened for its antioxidant activity due to phenolic and flavonoid contents, by employing radical scavenging assays; 2,2 -diphenyl, 1-picryl hydrazyl (DPPH) and nitric oxide. Ascorbic acid was used as a standard. Quantitative determination of phenols and flavonoids were carried out using spectrophotometric method. Total flavonoid content was determined as quercetin equivalent and total phenolic content was determined as pyrocatechol equivalent using Folin-Ciocalteu reagent. Plant produces more phenolic compounds than flavonoids. IC 50 value of methanol extract for DPPH free radical scavenging activity was found to be 292.7 μg, whereas for nitric oxide it was 204.61 μg. The result obtained in the present study indicates that the aerial parts of this plant are a rich source of natural antioxidants

Increased risk of coronary artery disease in diabetic persons is associated with increased level of lipoproteins. Usually, such risks are reverted with glycemic control by antidiabetic medicines in Type I diabetes millitus. However, in Type II diabetes mellitus lipid values can be improved using antidiabetics but still the risk of coronary artery disease remains. The initial approach for reducing lipid contents in diabetic patients should include glycemic control, diet, weight loss, and exercise. But if it fails then lipid-lowering agents like fibrate and HMG CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) inhibitors should work effectively. In the present study results of atorvastatin compared with biguanides proved atorvastatin as a more effective lipid-lowering agent along with antidiabetic activity so it can effectively help in reducing the risk of cardiovascular disease (CVD).

Omeprazole is widely prescribed in the form of enteric-coated formulations, due to the rapid degradation of the drug in the acidic condition of the stomach. In the current article, we are reporting the development and complete validation of a stability indicating chiral high-performance liquid chromatography (HPLC) method for the enantioselective analysis of omeprazole in the enteric-coated formulations. A precise and sensitive enantiomeric separation of omeprazole was obtained on Chiralcel OD-H analytical column (250mm × 4.6 mm, 5μm particle size) using normal phase chromatography. The analysis was performed under UV detection at 301nm wavelength. During method development, the addition of methanol to the mobile phase helped in getting the sharp peaks. The developed method showed linear response over a wide concentration range of 0.39-800μg/ml and the regression coefficients value (r 2 ) was obtained more than 0.999 for (S)- and (R)-omeprazole. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for (R)-omeprazole were found to be 0.39 and 0.78 μg/ml, respectively for 5 μl injection volume. The percentage recovery of (R)-omeprazole ranged from 93.5 to 104 in spiked formulation samples and omeprazole sample solution and mobile phase were found to be stable for at least 24 h at room temperature. The proposed method was found to be suitable and accurate for the quantitative determination of undesired enantiomer in the enteric-coated omeprazole formulations.